Pharmacokinetics and clinical efficacy of lorazepam in children with severe malaria and convulsions

Lorazepam (LZP) may be a more useful anticonvulsant to stop convulsions in children with severe malaria (SM) than diazepam, since it has a longer duration of action and can be given by other routes, such as intramuscular (i.m.).

There are no studies describing both the pharmacoknetics and clinical efficacy of LZP in African children, particularly those with SM.

We have undertaken a study with LZP, administered either intravenously (i.v.) or i.m., to children with SM and convulsions in order to describe and compare the pharmacokinetic profiles of LZP following administration via both routes and determine whether the currently recommended dose of LZP (0.1 mg kg−1) is effective in terminating convulsions in this group.

Administration of LZP (i.v. or i.m.) at the currently recommended dose (0.1 mg kg−1) resulted in rapid achievement of plasma LZP concentrations within the reported effective therapeutic range without clinically significant cardiorespiratory effects.

A single dose of LZP was effective in the rapid termination of convulsions in all children, and prevention of seizure recurrence for >72 h in 11 of 15 (73%) children and 10 of 11 (91%) children after i.v. and i.m. administration, respectively.